Not applicable.
Not applicable.
1. Field of the Invention
This invention relates generally to therapeutic painful stimuli such as electric pacing and subthreshold pulses, and more particularly to the process of reducing the pain associated with these therapeutic painful stimuli by modifying a patient""s pain perception and response using prepulse inhibition (PPI). Specifically, the present invention relates to reducing the pain and discomfort associated with painful transcutaneous and transesophageal cardiac pacing and subthreshold transcutaneous stimuli as provided using modern, noninvasive, transcutaneous or transesophageal pacing devices, either as stand-alone cardiac pacemakers, combination pacemaker-ECG monitors, or combination pacemaker-monitor-defibrillators.
2. Background Information
Implantable cardioverter-defibrillators (ICDs) deliver high-voltage electrical pulses (shocks) to terminate cardiac arrhythmias. This treatment is highly successful, but it is severely painful and may even stun a patient temporarily. Initially, painful and startling therapeutic shocks were considered acceptable only as a treatment of last resort. Because of this, ICD therapy was restricted to ventricular arrhythmias which were both life-threatening and refractory to all other therapies. Subsequently, however, ICDs have become first-line therapy for patients with a history of life-threatening ventricular arrhythmias and patients at risk for life-threatening ventricular arrhythmias. Controlled studies have shown that ICDs are superior to alternative therapy for specific groups of these patients. These studies are the Multicenter Automatic Defibrillator Implantation Trial (Moss et al, N Engl J Med 1996; 335: 1933-1940) and the Antiarrythmics Versus Implantable Defibrillators Trial (Zipes et al, N Engl J Med 1997; 337: 1576-1583).
As ICD therapy has been applied to larger numbers of patients with ventricular arrhythmias, more attention has been paid to the painful and startling nature of the therapeutic shocks and the psychological complications of this therapy. These factors limit patient acceptance of ICD treatment of arrhythmias in conscious patients. A significant fraction of patients report anxiety and fear of painful ICD shocks ((1) Dougherty, Psychological reactions and family adjustment in shock versus no shock groups after implantation of internal cardioverter defibrillator, Heart Lung 1995; 24: 281-291xe2x80x94(2) Dunbar et al, Cognitive therapy for ventricular dysrhythmia patients, J Cardiovasc Nursing 1997; 12: 33-44xe2x80x94(3) Luderitz et al, Patient acceptance of ICD devices: Changing attitudes, Am Heart J 1994; 127: 1179-1184xe2x80x94(4) Morris et al, Psychiatric morbidity following implantation of the automatic ICD, Psychosomatics 1991; 32: 58-64). Shocks correlate with anxiety, psychiatric morbidity and psychological distress in ICD recipients. In one study 87.5% of patients experienced xe2x80x9cnervousnessxe2x80x9d after a shock and 12.5% experienced xe2x80x9cterrorxe2x80x9d or xe2x80x9cfear.xe2x80x9d Patients who have experienced large numbers of repetitive shocks frequently suffer from a form of post-traumatic stress disorder.
Recently, ICD therapy has been applied to treatment of atrial arrhythmias, particularly atrial fibrillation ((1) Lau et al, Initial clinical experience with an implantable human atrial defibrillator, PACE 1997; 20: 220-225xe2x80x94(2) Timmersman et al, Early clinical experience with the Metrix automatic implantable atrial defibrillator, European Heart J 1997; 134). Although atrial fibrillation usually is not life-threatening, it is the most common arrhythmia requiring hospitalization in the United States. It causes potentially disabling symptoms of palpitations, shortness of breath, or chest pain and is an important cause of stroke.
The painful and startling nature of ICD shocks are considered a particular limitation for patient acceptance of ICD treatment of atrial fibrillation. It has been stated in recent published literature (Cooper et al, Internal atrial defibrillation in humans: Improved efficacy of biphasic waveforms and the importance of phase duration, Circulation 1997; 96: 2693-2700) that the ultimate acceptance of a fully automatic atrial defibrillator will depend on the reduction of pain to acceptable levels.
To this end, present state-of-the-art holds that a primary method of reducing the pain associated with these shocks is to reduce the strength of the shock pulse as measured by energy or voltage. This method requires a significant decrease in the shock strength required to defibrillate with a success rate of 50%. This shock strength is known as the defibrillation threshold. Recent studies have focused on reducing the atrial defibrillation threshold by altering the shape (waveform) of the delivered shock pulse or the locations of the electrodes (electrode configuration) through which these shocks are applied. The fundamental hypothesis is that lowering of the defibrillation threshold will permit atrial defibrillation with weaker shocks and thereby decrease the pain associated with these shocks in patients.
The shock strength judged tolerable for defibrillation in conscious patients has differed in previous studies, but is generally in the range of 0.1-0.5 joules (J). Zipes (Zipes et al, Clinical transvenous cardioversion of recurrent life-threatening ventricular tachyarrhythmias: Low energy synchronized cardioversion of ventricular tachycardia and termination of ventricular fibrillation in patients using a catheter electrode, Am Heart J 1982; 103: 789-794) reported that shocks of 0.5 J or less delivered between electrodes in the superior vena cava and right ventricle were tolerable for treatment of ventricular tachycardia. However, using the same electrode system, Perelman (Perelman et al, Assessment of prototype implantable cardioverter for ventricular tachycardia, Br Heart J 1984; 52: 385-391) found that 3 of 9 patients reported severe discomfort at a shock strength of 0.1 J. Nathan (Nathan et al, Internal transvenous low energy cardioversion for the treatment of cardiac arrhythmias, Br Heart J 1984; 52: 377) delivered transvenous shocks to 19 conscious patients for various atrial and ventricular arrhythmias. Fourteen of 19 patients described severe discomfort with shock strengths 0.5 J. Murgatroyd (Murgatroyd et al, Efficacy and tolerability of transvenous low energy cardioversion of paroxysmal atrial fibrillation in humans, J Am Coll Cardiol 1995; 25: 1347-1353) determined the range of tolerable shock strengths for the most favorable electrode configuration for atrial defibrillation (right atrium to distal coronary sinus). Although the range of shock strengths tolerated without severe discomfort was 0.1 to 1.2 J, seven of 19 patients found even 0.1 J shocks intolerable. Using a different electrode system, Steinhaus (Steinhaus et al, Atrial defibrillation: are low energy shocks acceptable to patients? PACE 1996; 19: 625) delivered shocks of 0.4 J and 2.0 J shocks in randomized order. Patients reported no difference in perceived pain between the two shock strengths. Both shock strengths were given discomfort scores of approximately 7 on a scale of 0-10.
However, Steinhaus found that the second shock was judged significantly more painful than the first shock, independent of shock strength. This observation is important because a strategy for reducing pain in defibrillation of arrhythmias which are not life-threatening (such as atrial fibrillation) contemplates clinical use of defibrillation shocks with strength near the defibrillation threshold. The hypothesis is that, even if multiple shocks are required to terminate the arrhythmia, multiple weaker shocks will be better tolerated than one strong shock. Steinhaus"" data suggest that any clinical benefit in pain reduction achieved by delivering clinical defibrillation shocks with strength near the defibrillation threshold is likely to be offset by the increased discomfort associated with subsequent shocks as weak as 0.4 J.
Data reported for atrial defibrillation thresholds must be considered in the perspective of these reported values for tolerable shock strengths. Cooper (Cooper et al, Internal cardioversion of atrial fibrillation in sheep, Circulation 1993; 87: 1673-1686) measured the atrial defibrillation threshold for multiple waveforms and electrode configurations in sheep. They showed that a specific biphasic waveform (3 ms phase 1 and 3 ms phase 2) and a specific electrode configuration (right atrial appendage to distal coronary sinus) resulted in the lowest atrial defibrillation threshold for the combinations of electrode configurations and waveforms tested (1.3xc2x10.4 J). However, use of this waveform and electrode configuration in humans with paroxysmal (intermittent) atrial fibrillation, the principal treatment population for atrial ICDs, resulted in atrial defibrillation thresholds approximately twice as high as in sheep. Johnson (Johnson et al, Circulation 1993; I 592) reported a value of 2.5xc2x11.4 J and Murgatroyd (Murgatroyd et al, J Am Coll Cardiol 1995; 25: 1347-1353) reported a value of 2.2xc2x11.0 J. Therefore, the prior art does not teach a method sufficient for the reduction of a patient""s perceived pain during atrial defibrillation shocks.
More recently, Cooper (Cooper et al, Internal cardioversion of atrial fibrillation: Marked reduction in defibrillation threshold with dual current pathways, Circulation 1997; 96: 2693-2700) showed that sequential shocks delivered through two different sets of electrodes significantly decreased atrial defibrillation thresholds in sheep. The defibrillation threshold for this complex method (0.36xc2x10.13 J) was significantly lower than that of the best single-pathway method (1.3xc2x10.3 J). Since the average atrial defibrillation thresholds in sheep are approximately half that of the average atrial defibrillation thresholds for patients with paroxysmal atrial fibrillation, it was estimated that this newly determined method would provide average atrial defibrillation thresholds of slightly less than 1 J in patients. Thus, despite the additional complexity of the implant procedure and possible additional short and long-term morbidity associated with this new method, it is not likely to permit atrial defibrillation shocks without severe discomfort in the majority of patients. Therefore, this prior art does not teach a method sufficient for the significant reduction of a patient""s perceived pain during atrial defibrillation. This prior art moreover requires the increased cost, surgical complexity, and risk associated with two additional electrodes.
The method and apparatus of U.S. Pat. No. 5,332,400 issued to Alferness discloses an implantable atrial defibrillator that provides a warning to a patient prior to delivery of an atrial shock pulse to cardiovert or defibrillate the patient""s atrial arrhythmia. The atrial defibrillator applies a warning electrical shock to the patient""s atria when the apparatus determines that the atria require cardioversion or defibrillation. The warning shock has an energy level lower than that required to treat the arrhythmia but high enough to be discerned by the patient without pain or other discomfort. The purpose of this warning is to provide sufficient time in advance of the therapeutic shock (in the range of 1 to 20 minutes) to afford a patient the opportunity to prepare for this painful and startling therapy. The Alferness method and apparatus demonstrate the limitation of the prior art to significantly reduce the extreme pain perceived by a patient when the defibrillation therapy is applied.
The method and apparatus of U.S. Pat. No. 5,439,481 issued to Adams discloses an implantable atrial and ventricular defibrillator that diagnoses atrial and ventricular arrhythmias, automatically treats the ventricular arrhythmias, but allows discretionary treatment of the atrial arrhythmias. Such discretionary control permits the patient to forego painful atrial defibrillation shocks based on a medical assessment that the atrial arrhythmia is not significantly dysfunctional and is amenable to less immediate and less urgent medical treatment. The Adams method and apparatus further demonstrate the limitation of the prior art to alleviate the extreme pain perceived by a patient when atrial defibrillation therapy is applied.
The method and apparatus of U.S. Pat. No. 5,630,834 issued to Bardy discloses an implantable atrial defibrillator that determines whether a patient is asleep prior to delivery of an atrial shock pulse. Defibrillation shocks that would be extremely painful to a conscious patient are delivered only when a patient is asleep. Bardy states that although numerous patents and applications attempt to optimize shock waveforms and electrode systems to reduce defibrillation thresholds (and therefore pain), the reliable accomplishment of low thresholds for all patients will remain a difficult and perhaps infeasible objective. This method may require a patient to remain in atrial fibrillation for many hours until the patient falls asleep. Thus it is not practical for some patients who become symptomatic shortly after the onset of atrial fibrillation or for patients with ventricular arrhythmias who typically require treatment as soon as possible after the onset of the arrhythmia. Further, some patients have reported being awakened from sleep by painful and startling ICD shocks. Thus, administration of shocks during sleep is painful in some patients. In addition, a patient""s knowledge that he/she may be shocked while asleep may result in anticipatory anxiety that interferes with sleep. The Bardy method and apparatus further demonstrate the limitation of the prior art to significantly reduce the extreme pain perceived by a conscious patient when defibrillation therapy is applied.
We therefore describe a method and apparatus to significantly diminish or eliminate the perceived pain by reducing the perceived intensity of defibrillation shocks and by inhibiting the startle response associated with these shocks. The clinical basis for the invention is the fundamental physiologic principal of PPI. As will be appreciated from a review of the background discussion and the detailed description of the preferred embodiments, the invention overcomes the limitations and shortcomings of the prior art.
In the field of neurophysiologic and neuropsychiatric research, it has been long appreciated that the experienced intensity of a strong, abrupt stimulus, and the behavioral (startle) response to this stimulus can be diminished by delivering a weak stimulus 30-500 ms prior to the strong stimulus ((1) Cohen et al, Sensory magnitude estimation in the context of reflex modification, J Exper Psychology 1981; 7: 1363-1370xe2x80x94(2) Swerdlow et al, xe2x80x9cNeurophysiology and neuropharmacology of short lead interval startle modification,xe2x80x9d Chapter 6 of Startle Modification: Implications for Neuroscience Cognitive Science, and Clinical Science, Dawson et al, Cambridge Univ Press, 1997). This physiologic suppression of the startle reflex is referred to as prepulse inhibition (PPI). PPI decreases both the motor (startle) response and the subject""s perception of the intensity of the startling stimulus (pain). Normal human subjects consistently rate startling stimuli as significantly less intense if these stimuli are preceded by an appropriate weak prestimulus than if they were presented alone.
The neural circuitry responsible for the sensorimotor modulation of PPI has been studied extensively. These studies indicate that PPI reflects the activation of ubiquitous, xe2x80x9chard-wired,xe2x80x9d behavioral gating processes that are regulated by forebrain neural circuitry. PPI occurs in virtually all mammals, and can be elicited in humans and humans and experimental animals using near-identical stimuli to produce strikingly similar response patterns (Swerdlow et al, Assessing the validity of an animal model of deficient sensorimotor gating in schizophrenic patients, Arch Gen Psychiatry 1994; 51: 139-154). The importance of these findings is that optimal stimulus parameters for PPI, and the neural substrates that regulate PPI, can be studied easily in animal models. This capability facilitates the application of PPI principles as disclosed in the preferred embodiments of the invention.
In one preferred embodiment of the invention, a single, low-voltage, short-duration pulse (the prepulse) precedes a high-voltage shock pulse. The time interval between the prepulse and the shock pulse is set between 30 to 500 ms. The specific time interval is determined by a testing method which identifies the optimal interval for PPI. The prepulse and therapeutic shocks may have arbitrary waveforms which are not necessarily identical. For example, these may include monophasic or biphasic capacitive-discharge pulses of the type presently used in ICDs, or a pulse waveform constructed specifically to reduce pain, such as a rounded, slow-rise time, or ascending ramp waveform (Mouchawar et al, Sural nerve sensory thresholds of defibrillation waveforms, J Amer Coll Card 1998; 31(Suppl A): 373). At the time of implant of an atrial, ventricular, or dual-chamber ICD with the invention incorporated therein, a physician first determines an appropriate electrode system for a given patient and the appropriate cardioversion or defibrillation energy setting for that patient and electrode system. The physician then adjusts the amplitude of the prepulse and intervening time interval between the prepulse and the therapeutic shock pulse so as to significantly reduce or eliminate the patient""s perceived pain and startle response caused by the shock pulse. Typically, the shock strength required for cardioversion or defibrillation is determined while the patient is under the influence of a short-acting anesthetic. The prepulse amplitude and time interval are adjusted in the conscious patient after the effects of any short-acting anesthetic has dissipated. Alternatively, the prepulse amplitude and time interval are adjusted at a postoperative programming study.
It is important to note that defibrillation shocks are associated with a prominent startle responses in many patients. Studies of other types of startle responses demonstrate that startle responses are actually increased when warning stimuli preceded the startling stimuli at intervals ( greater than 1 sec) that are adequate to evoke conscious anticipation of the startling stimulus (prepulse facilitation). Thus a xe2x80x9cwarningxe2x80x9d prestimulus which is sufficiently early to evoke a conscious response prior to an ICD shock is likely to increase the shock-induced startle effect. ICD recipients report severe discomfort related specifically to the startling effects of defibrillating shocks. A long-delay xe2x80x9cwarningxe2x80x9d prestimulus is a programmable option in some ICDs. This feature is rarely activated because patients experience anxiety during the anticipatory interval following the xe2x80x9cwarningxe2x80x9d prestimulus. The invention overcomes these problems by suppressing the painful xe2x80x9cjoltxe2x80x9d associated with the defibrillation-induced startle reflex, using automatic, preconscious mechanisms evoked during a time interval (30-500 ms) which is too short to stimulate anticipatory anxiety.
The methods and devices of the prior art that most nearly approach the novel features of the invention, which uses PPI to reduce the perceived pain of therapeutic electrical stimuli delivered to a conscious patient, are, in fact, quite remote from it. Their marginal relevance can best be appreciated by a short, comparative description.
The method and apparatus of U.S. Pat. Nos. 5,314,448 and 5,366,485 issued to Kroll and Adams disclose electrical pretreatment to a ventricular fibrillating heart to permit the applied shock pulse to defibrillate the ventricles with less energy than may otherwise be required. Pretreatment pulses and the treatment shock are delivered through the same electrodes. The underlying hypothesis asserts that electrical pretreatment of a fibrillating heart is expected to achieve temporal organization of the ventricular cardiac cells, thereby diminishing the demands imposed on the defibrillation threshold for the defibrillating shock pulse. As will become apparent in the description of the preferred embodiments, the invention differs significantly from this prior art. The concept of electrical pretreatment of a fibrillating heart to assist the defibrillating shock pulse by reducing its level of required energy through temporal cardiac organization is completely absent from the invention.
The method and apparatus of U.S. Pat. No. 5,425,749 issued to Adams discloses the delivery of an electrical preemptive cardioversion shock to a patient determined to have a life-threatening arrhythmia such as ventricular fibrillation. The underlying hypothesis asserts that the shock strength required for defibrillation is directly related to the duration of fibrillation and that an electrical preemptive shock delivered as soon as possible following the onset of an arrhythmia will reduce the total energy requirements for cardioversion or defibrillation. The preemptive shock is thus delivered several seconds before the main cardioverting or defibrillating pulse. As will become apparent in the description of the preferred embodiments, the invention differs significantly from this prior art. The concept of electrical preemptive cardioversion or defibrillation to quickly treat a patient and thereby to significantly reduce the size and energy requirements of a defibrillator is completely absent from the invention.
Despite the need in the art for an ICD apparatus or methods which overcome the shortcomings and limitations of the prior art, none insofar as is known has been developed or proposed. Accordingly, it is an object of the invention to provide an implantable atrial, ventricular, or dual-chamber ICD method and apparatus that applies the clinical science related to sensorimotor gating to reduce or eliminate the perceived intensity of, and startle response to, the ICD""s shock pulse. The invention reduces or eliminates the pain by delivering a timed prepulse that reduces the perceived intensity of the shock pulse, and inhibits the startle response to the shock pulse. There are no such teachings in the prior art.
3. Background Information of Present Invention
Patients often require emergency cardiac pacing in the form of temporary transcutaneous or transesophageal electrical pulses. Transcutaneous cardiac pacing (TCP) is commonly used in emergency medicine for immediate treatment of unstable bradycardia until a transvenous pacemaker can be established under more controlled circumstances. Transcutaneous or transesophageal cardiac pacing (TEP) may also be used to provide cardiac electrical activation during asystolic cardiac arrest as an adjunct to cardiopulmonary resuscitation in either in-hospital or out-of-hospital settings. These techniques may also be used to terminate ventricular or supraventricular arrhythmias through overdrive pacing or other antitachycardia pacing methods.
Rapid TEP atrial pacing is used with increasing frequency in conscious patients to perform cardiac stress tests using echocardiographic or scintigraphic imaging ((1) Iliceto S et al, Prediction of cardiac events after uncomplicated myocardial infarction by cross-sectional echocardiography during transesophageal atrial pacing, Int J Cardiol 1990; 28: 95-103, (2) Anselmi M et al, Usefulness of transesophageal atrial pacing combined with two-dimensional echocardiography (echo-pacing) in predicting the presence and site of residual jeopardized myocardium after uncomplicated acute myocardial infarction, Am J Cardiol 1994; 73: 534-538, (3) Anselmi M et al, Comparison of left ventricular function and volumes during transesophageal atrial pacing combined with two-dimensional echocardiography in patients with syndrome X, atherosclerotic coronary artery disease, and normal subjects, Am J Cardiol 1997; 80: 1261-1265, (4) Marangelli V et al, Detection of coronary artery disease by digital stress echocardiography: comparison of exercise, transesophageal atrial pacing and dipyridamole echocardiography, J Am Coll Cardiol 1994; 24: 117-124, (5) Marinsky G et al, Diagnostic value of synchronized transesophageal atrial pacing, PACE 1991, 14: 1228-1232, (6) Matiushin GV et al, [Combined use of left atrial transesophageal pacing and cordarone in atrial flutter], Ter Arkh 1998; 70: 71-73, (7) Santomauro M et al, Diagnosis of coronary artery disease with Tc 99 m-methoxy isobutyl isonitrile and transesophageal pacing, Angiology 1992; 43: 818-825). However, the pain associated with this method has proved an important issue.
TEP may also be used in conjunction with recording of the esophageal ECG as a simple and noninvasive means of diagnosing the mechanisms of cardiac rhythm disturbances (Deal B J, Chapter 35, Esophageal pacing, in: Ellenbogen K A et al, Clinical Cardiac Pacing, Philadelphia, Pa., W B Saunders Company, 1995, 701-705). TEP has also been used as a method of temporary pacing in patients who have required removal of infected transvenous pacemaker electrodes or those undergoing magnetic resonance imaging (Hofman M B et al, Transesophageal cardiac pacing during magnetic resonance imaging: feasibility and safety considerations, Magn Reson Med 1996; 35: 413-422).
It is well known in the art that the first method for external temporary cardiac pacing was introduced in 1952 by Zoll (Zoll P M, Resuscitation of the heart in ventricular standstill by external electrical stimulation, N Engl J Med 1952; 247: 768-771). Zoll developed the first reported transcutaneous cardiac pacemaker comprising an external DC pulse generator, a 2 ms pulse duration, and 3 cm diameter metal paddles. Zoll applied the device to patients suffering from asystole due to bradycardia. Discomfort and pain, however, from cutaneous nerve stimulation, pectoralis muscle contraction, and local soft tissue damage proved intolerable to many conscious patients. Despite its demonstrated efficacy, the procedure was abandoned because of these side effects in favor of newly developed transvenous pacing.
Except for patients undergoing cardiac surgery, transvenous pacing is usually accomplished by placement of transvenous pacemaker leads through the internal jugular, subclavian, femoral, or antecubital veins. Significant complications can arise from these procedures, particularly in hemodynamically unstable patients. Technological advances in the methods of TCP demonstrated that it was safe, effective, easy to use, reduced the pain and discomfort in some patients, and produced hemodynamic responses similar to those produced by right ventricular endocardial pacing (Zoll P M et al, External noninvasive temporary cardiac pacing: clinical trials, Circulation 1985; 71: 937-944). These improvements lead to a resurgence of TCP use due to inadequacies of transvenous pacing in the setting of cardiac arrest, asystole, and cardiopulmonary resuscitation. TCP improvements include (1) large surface area electrodes and (2) longer duration, lower intensity, constant-current pacing pulses.
Despite these improvements in the art of TCP, there were no significant reductions in the associated pain and discomfort. A trial using a TCP device focused on patients with third-degree atrioventricular block or asystole due to acute myocardial infarction requiring acute need for pacing or patients with third-degree atrioventricular block requiring a permanent implanted pacemakers either immediately or within 1-3 days (Madsen J K et al, Transcutaneous pacing: experience with the Zoll noninvasive temporary pacemaker, Am J Heart 1988; 116: 7-10). The researchers used a Zoll TCP device, which functioned as VVI demand pacemaker with separate pacing and sensing electrodes. The apparatus contained a pacing unit, an ECG monitor, screen, and paper recorder. The pacing pulse was a rectilinear constant current pulse of 40 ms duration and the amplitude varied from 0 to 140 mA. Pacing was achieved by two electrodes, one placed mid-chest (anterior apex) and one placed on mid-back (posterior). The front electrode was 75 cm2 and the back electrode was 140 cm2 in area. The Zoll TCP device contained all the presently known improvements. Regardless, pain and discomfort were felt by most patients to varying degrees. Some patients felt unacceptable pain at 40 mA and other patients felt slight irritation at pacing pulse of 80 mA. It was determined that 20 mA caused a prickly sensation of the skin, 40 mA was felt as a definite thump, 60 mA was slightly painful, and 80 mA was definitely painful. The median threshold for pacing determined for the patients in the trial was 55 mA, ranging from 30 to 110 mA. Sixteen of 29 conscious patients (55%) felt chest pain with threshold pacing. Sedation or analgesics were necessary for these patients, and it was the impression of the research physicians that sedation is required for any TEP output above 50 mA. Thus, to achieve a reliable safety margin, usually considered to be 1.5-2xc3x97 the pacing threshold, the vast majority of patients require sedation.
Patient tolerance was measured in a second study using the Zoll TCP device (Klein L S et al, Transcutaneous pacing: patient tolerance, strength interval relations and feasibility for programmed electrical stimulation, Amer J Cardiol 1988; 62: 1126-1129). Ventricular pacing thresholds using TCP were determined in 11 of 16 patients. Thresholds could not be determined in 5 patients due to intolerable chest discomfort. In addition, 3 of the 11 patients in whom threshold was obtained could not tolerate the pacing for the duration required to complete the study. Therefore, only 8 of the 16 patients tolerated TCP in this study, and only one of these 8 patients tolerated pacing at more than 20 mA above threshold. The mean threshold was 61 mA (ranging from 45 mA to 80 mA) for these 8 patients. The three patients in whom threshold was obtained but were unable to tolerate the TCP had a mean threshold of 88 mA. The conclusions drawn were that TCP was not well tolerated, 15 of the 16 patients received conscious sedation, and therefore TCP appeared to be limited to a subset of patients with LOW TCP thresholds.
Subjective discomfort levels were measured in a third study using a Marquette combination defibrillator-monitor-pacing device (Chapman P D et al, Efficacy and safety of transcutaneous low-impedance cardiac pacing in human volunteers using conventional polymeric defibrillation pads, Ann Emerg Med 1992; 21: 1451-1453). Thirty healthy unmedicated adult volunteers were paced transcutaneously to the threshold of capture and beyond by an intensity factor of 125%. Pacing was continued at the 125% level for two minutes, during which subjective discomfort levels were recorded on a 1 (minimal) to 5 (severe) pain scale. The pain assessment averaged 3.2, placing the mean discomfort level between moderate discomfort and moderately severe discomfort.
The fact that pain is a limiting factor in TCP has been verified in multiple other studies. In a typical study by Altamura (Altamura G et al, Treatment of ventricular and supraventricular tachyarrhythmias by transcutaneous cardiac pacing, PACE 1989; 12: 331-338), the efficacy of TCP in the treatment of tachyarrhythmic events was evaluated. The experiment results showed that TCP was easily usable and immediately successful in the majority of atrioventricular reentrant tachycardias and a relevant percentage of ventricular tachycardias. However, even though Altamura reported no clinically significant untoward effects, the clinical protocol was purposefully designed to minimize the painful discomfort of the overdrive pacing and the results showed that the pacing was modestly tolerable if used for only a few seconds. Therefore, these devices demonstrate the limitation of the prior art to significantly reduce the extreme pain perceived by a conscious patient when transcutaneous or transesophageal therapy is applied.
Hence, the pain and discomfort of TCP is well recognized in the medical community. Despite this matter, TCP has been demonstrated to be safe and efficacious across a wide range of important clinical circumstances and pacing modalities. The pacing parameters have not changed significantly since an improved version was clinically evaluated as reported by Zoll in 1985. TCP is routinely combined with a defibrillator to provide a complete cardiac arrest intervention system, offering antibradycardia and antitachycardia pacing combined with an external defibrillation capability. This configuration results in a complete system connected with a single set of multifunction electrodes performing detection, pacing, and defibrillation. The pacing programmability range of available devices are pulse durations from 5 ms to 55 ms, current amplitude from 0 mA to 210 mA, and pacing rates from 30 to 180 ppm. The energy programmability is used to set the energy level at slightly above the pacing threshold to minimize discomfort to conscious patients. Therefore, pacing programmability has broadened the applications of TCP in conscious patients, in spite of the patient""s possibly severe pain and discomfort (Trigano J A et al, Noninvasive transcutaneous cardiac pacing: modern instrumentation and new perspectives, PACE 1992; 15: 1937-1943). Most importantly, the clinical application of this kind of system is now incorporated into the standard cardiac life support guidelines (Standards and guidelines for cardiopulmonary resuscitation (CPR) and emergency cardiac care (ECC), Am Med Assoc 1986; 255: 2905-2898). Specifically, the use of TCP for emergency cardiac pacing is described in Chapter 5 of the 1997 Textbook of Advanced Cardiac Life Support, and this chapter is hereby incorporated by reference in its entirety.
The methods and devices of the prior art that most nearly approach the novel features of the present invention, which uses PPI to reduce the perceived pain of therapeutic electrical stimuli delivered to a conscious patient, are, in fact, quite remote from it. Their marginal relevance can best be appreciated by a short, comparative description.
The method and apparatus of U.S. Pat. No. 4,349,030 issued to Belgard discloses a pulse generator that provides external noninvasive cardiac stimulation through design improvements comprising constant-current, spikeless electrical pulses with durations greater than 5 ms and large-surface, non-metallic, skin-contacting electrodes. With these design improvements focused on delivering a low current density, it was proposed that the pulse generator and its preferred embodiments would overcome the limitations of the prior art by eliminating local sensory nerve stimulation and strong skeletal muscle contraction. The purpose of eliminating these effects was to reduce the extreme pain perceived by a patient when TCP is applied. However, this method and apparatus are the Zoll TCP device evaluated in the clinical reports discussed above ((1) Madsen J K, Am J Heart 1988; 116: 7-10, (2) Klein L S, Amer J Cardiol 1988; 62: 1126-1129). The clinical reports clearly demonstrated the limitation of this prior art to significantly reduce the pain and discomfort perceived by a patient.
In a series of U.S. Pat. Nos. 5,193,537, 5,205,284, 5,282,843, and 5,431,688 each issued to Freeman, a general method and apparatus is disclosed regarding transcutaneously pacing the heart with background stimuli occurring in the intervals between pacing stimuli to reduce patient discomfort during pacing. The patents disclose a method and apparatus that feature a pacing pulse comprising of a series of pulses in which each pulse has a duration and amplitude that does not permit it to stimulate either skeletal or cardiac muscle. It is proposed that when these pulses are placed close enough together during output to form the equivalent of a single pacing pulse the series of pulses will capture the heart while reducing skeletal muscle stimulation. However, it is well known that the reduction of the skeletal muscle stimulation is highly variable and is extremely sensitive to electrode placement on a patient, particularly athletes and patients with medium to highly defined muscular structure. The overall reduction of skeletal muscle stimulation is no more than 5%-10% and has a nonlinear relationship to a patient""s perceived pain. The patents further disclose a method and apparatus that feature background stimuli in the intervals between pacing stimuli. These background pulse trains are proposed to enhance accommodation of skeletal muscle and cutaneous nerves and discourage accommodation of cardiac muscle, thereby decreasing skeletal muscle and cutaneous nerve stimulation while simultaneously achieving effective stimulation of the heart. However, as discussed in the background and clinical sections of the present invention, the combination of pacing and background pulse trains delivered by Freeman""s apparatus in its preferred embodiments will in fact intensify the patient""s perception of pain, particularly for two or more pacing pulses and for time periods greater than 1 second. Thus, the Freeman method and apparatus further demonstrate the limitation of prior art to significantly reduce the pain and discomfort perceived by a patient during transcutaneous or transesophageal cardiac stimulation.
More recently, the method and apparatus of U.S. Pat. No. 5,782,882 issued to Lerman discloses a TCP system that includes a transcutaneous electrical nerve stimulation system (TENS) coupled to the TCP system to concurrently apply nerve stimulation pulses to the patient. The nerve stimulation pulses are proposed to mitigate any discomfort that a patient may experience from the TCP. Again, as discussed in the background and clinical sections of the present invention, the combination of pacing pulses with TENS as delivered by Lerman""s apparatus in its preferred embodiments will in fact intensify the patient""s perception of pain, particularly for two or more pacing pulses and for time periods greater than 1 second. Thus, the Lerman method and apparatus further demonstrate the limitation of prior art to significantly reduce the pain and discomfort perceived by a patient during transcutaneous or transesophageal cardiac stimulation.
We therefore describe a method and apparatus to significantly diminish or eliminate the perceived pain by reducing the perceived intensity of transcutaneous or transesophageal cardiac pacing and by inhibiting the startle response associated with these pulses. The clinical basis for the present invention is the fundamental physiologic principal of PPI as described in the background section above and the clinical section of the preferred embodiment below. As will be appreciated from a review of the background discussion and the detailed description of the preferred embodiments, the present invention overcomes the limitations and short-comings of the prior art.
The present invention provides a method and apparatus to pretreat a patient prior to a therapeutic painful stimulus, comprising the step of applying at least one pain inhibiting stimulus to a first part of a patient""s body prior to an application of the therapeutic painful stimulus to the same part or a second part of a patient""s body. This method is intended primarily for use in conscious patients, but it may also be used in sleeping patients.
The benefits of this invention will become clear and will be best appreciated with reference to the detailed description of the preferred embodiments. Other objects, advantages and novel features will be apparent from the description when read in conjunction with the appended claims and attached drawings.